## First-Line Induction Therapy in Ulcerative Colitis **Key Point:** Mesalamine (5-aminosalicylic acid) is the first-line agent for inducing remission in mild-to-moderate ulcerative colitis, both as monotherapy and in combination with topical agents. ### Mechanism of Action - Anti-inflammatory effect via inhibition of nuclear factor-kappa B (NF-κB) - Reduces prostaglandin synthesis and leukocyte recruitment - Acts locally on colonic mucosa ### Dosing and Route in UC - **Oral:** 2–4 g daily in divided doses (maintenance: 1.5–2.4 g daily) - **Topical (rectal):** Enema or suppository for distal disease - **Combination:** Oral + topical for better efficacy in moderate disease ### Efficacy Data - Remission induction rate: 40–50% in mild-to-moderate UC - Superior to placebo in multiple RCTs - Also effective for maintenance of remission ### When to Escalate | Disease Severity | First-Line | Second-Line | |---|---|---| | Mild-moderate | 5-ASA (oral ± topical) | Add corticosteroids | | Moderate-severe | 5-ASA + corticosteroids | Add biologics (TNF-α inhibitors) | | Severe/fulminant | IV corticosteroids ± biologics | Consider colectomy | **High-Yield:** Mesalamine is safe, well-tolerated, and effective for both induction and maintenance in UC. It is NOT effective in Crohn's disease. **Clinical Pearl:** Topical mesalamine (enema) penetrates 15–20 cm proximally; suppository reaches only the rectosigmoid. Combination therapy (oral + topical) is superior to oral alone in distal/left-sided disease. ### Monitoring - Baseline renal function (rare nephrotoxicity) - Clinical response at 4–6 weeks - If inadequate response → add corticosteroids or escalate to biologics [cite:Harrison 21e Ch 297]
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